Comparison of anticancer effects of a novel histone deacetylase (HDAC) inhibitor CG200745 and SAHA in non-small lung cancer cells

Histone deacetylase (HDAC) inhibition offers the potential for anti-cancer effects in a variety of cancers, since HDAC plays an important role in cancer development and progression. Thus, we demonstrated the therapeutic efficacy of the new HDAC inhibitor, CG200745, in comparison with existing HDAC inhibitors, such as suberoylanilide hydroxamic acid (SAHA) in non-small lung cancer cells.Compared with SAHA, CG200745 had inhibited cell viability and HDACs expression, and induced apoptosis, ROS and mitochondrial dysfunction. CG200745 also significantly reduced tumor volume in vivo compared with SAHA. We observed increased apoptosis and ROS after treatment with survivin siRNA and CG200745, whereas overexpression of survivin protected against apoptosis and ROS by CG200745. We next demonstrated that CG200745 reduced the acetylation of survivin and that survivin is present in the nucleus. CG200745 showed a decrease in the stability of survivin. Furthermore, CG200745 increased expression of actylated-p53 and decreased activity of survivin promoter. We found that -189 ~ -11 plays an important role in the p53 binding site of the survivin promoter, and binding of p53, is increased depending on the CG200745 concentration. Collectively, these data shows that CG200745 induces apoptosis more than SAHA through down-regulation of survivin in NSCLC cells. CG200745 reduces the stability of survivin by inhibiting deacetylation of survivin, and decreases the promoter activity of survivin by acetyl...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Lung cancer Source Type: research